99mTc labelled complexes with secnidazole xanthate: Synthesis and evaluation as potential radiotracers to target tumor hypoxia

Xiao Lin; Qing Ruan; Xuran Zhang; Xiaojiang Duan; Yanguo Teng; Junbo Zhang

doi:10.1016/j.apradiso.2018.07.036

^99mTc labelled complexes with secnidazole xanthate: Synthesis and evaluation as potential radiotracers to target tumor hypoxia

Appl Radiat Isot. 2018 Oct:140:289-293. doi: 10.1016/j.apradiso.2018.07.036. Epub 2018 Jul 30.

Authors

Xiao Lin¹, Qing Ruan², Xuran Zhang³, Xiaojiang Duan², Yanguo Teng⁴, Junbo Zhang⁵

Affiliations

¹ College of Water Sciences, Beijing Normal University, No 19, Xinjiekouwai Street, Beijing 100875, PR China; Key Laboratory of Radiopharmaceuticals (Beijing Normal University), Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, PR China.
² Key Laboratory of Radiopharmaceuticals (Beijing Normal University), Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, PR China.
³ Key Laboratory of Radiopharmaceuticals (Beijing Normal University), Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, PR China; Department of Isotopes, China Institute of Atomic Energy, Beijing 102413, PR China.
⁴ College of Water Sciences, Beijing Normal University, No 19, Xinjiekouwai Street, Beijing 100875, PR China.
⁵ Key Laboratory of Radiopharmaceuticals (Beijing Normal University), Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, PR China. Electronic address: [email protected].

PMID: 30092554
DOI: 10.1016/j.apradiso.2018.07.036

Abstract

In this study, the commercially available secnidazole was successfully converted to secnidazole xanthate (SNXT), in which the xanthate group can act as a bifunctional chelator to coordinate with ^99mTc. ^99mTc-nitrido complex of SNXT(^99mTcN-SNXT) and ^99mTc-oxo complex of SNXT(^99mTcO-SNXT) were prepared with high radiochemical purity. Both of the complexes were found to be stable in vitro and to exhibit similar hydrophilicity. In addition, comparative in vitro cell uptake studies under anoxic and normoxic conditions demonstrated that both agents were preferentially taken up by hypoxic cells. Biodistribution studies in mice bearing S180 tumor showed ^99mTcO-SNXT exhibited a higher tumor uptake and tumor-to-muscle ratio than ^99mTcN-SNXT. Furthermore, in SPECT imaging study, ^99mTcO-SNXT exhibited a clear accumulation in tumor at 2 h post-injection, suggesting its potential to be a novel hypoxia imaging agent.

Keywords: Nitroimidazole; SPECT; Secnidazole; Technetium-99m; Tumor hypoxia.

MeSH terms

Animals
Biological Transport, Active
Cell Line, Tumor
Drug Stability
Female
Metronidazole / analogs & derivatives*
Metronidazole / chemical synthesis
Metronidazole / chemistry
Metronidazole / pharmacokinetics
Mice
Organotechnetium Compounds / chemical synthesis*
Organotechnetium Compounds / chemistry
Organotechnetium Compounds / pharmacokinetics
Radiopharmaceuticals / chemical synthesis*
Radiopharmaceuticals / chemistry
Radiopharmaceuticals / pharmacokinetics
Sarcoma 180 / blood
Sarcoma 180 / diagnostic imaging*
Sarcoma 180 / metabolism
Tissue Distribution
Tomography, Emission-Computed, Single-Photon / methods
Tumor Hypoxia* / physiology

Substances

Organotechnetium Compounds
Radiopharmaceuticals
Metronidazole
secnidazole